Hematopoietic stem cells (HSCs) emerge during development from the vascular wall of the main embryonic arteries. The onset of circulation triggers several processes that provide critical external factors for HSC generation. Nevertheless, it is not fully understood how and when the onset of circulation affects HSC emergence. Here we show that in Ncx1−/− mouse embryos devoid of circulation the HSC lineage develops until the phenotypic pro-HSC stage. However, these cells reside in an abnormal microenvironment, fail to activate the hematopoietic program downstream of Runx1, and are functionally impaired. Single-cell transcriptomics shows that during the endothelial-to-hematopoietic transition, Ncx1−/− cells fail to undergo a glycolysis to oxidative phosphorylation metabolic switch present in wild-type cells. Interestingly, experimental activation of glycolysis results in decreased intraembryonic hematopoiesis. Our results suggest that the onset of circulation triggers metabolic changes that allow HSC generation to proceed.

Azzoni, E., Frontera, V., Anselmi, G., Rode, C., James, C., Deltcheva, E., et al. (2021). The onset of circulation triggers a metabolic switch required for endothelial to hematopoietic transition. CELL REPORTS, 37(11) [10.1016/j.celrep.2021.110103].

The onset of circulation triggers a metabolic switch required for endothelial to hematopoietic transition

Azzoni, Emanuele
Primo
;
Barone, Cristiana;
2021

Abstract

Hematopoietic stem cells (HSCs) emerge during development from the vascular wall of the main embryonic arteries. The onset of circulation triggers several processes that provide critical external factors for HSC generation. Nevertheless, it is not fully understood how and when the onset of circulation affects HSC emergence. Here we show that in Ncx1−/− mouse embryos devoid of circulation the HSC lineage develops until the phenotypic pro-HSC stage. However, these cells reside in an abnormal microenvironment, fail to activate the hematopoietic program downstream of Runx1, and are functionally impaired. Single-cell transcriptomics shows that during the endothelial-to-hematopoietic transition, Ncx1−/− cells fail to undergo a glycolysis to oxidative phosphorylation metabolic switch present in wild-type cells. Interestingly, experimental activation of glycolysis results in decreased intraembryonic hematopoiesis. Our results suggest that the onset of circulation triggers metabolic changes that allow HSC generation to proceed.
Articolo in rivista - Articolo scientifico
hematopoiesis, embryo, development, hematopoietic stem cells, metabolism, mouse, hemogenic endothelium, circulation;
English
2021
37
11
110103
open
Azzoni, E., Frontera, V., Anselmi, G., Rode, C., James, C., Deltcheva, E., et al. (2021). The onset of circulation triggers a metabolic switch required for endothelial to hematopoietic transition. CELL REPORTS, 37(11) [10.1016/j.celrep.2021.110103].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/341099
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